HIV-1 INFECTION MODULATES CD4+ T CELL GENE EXPRESSION TO INDUCE A QUIESCENT PHENOTYPE

The largest barrier to treatment of HIV-1 infection is the establishment of a viral reservoir constituted mostly by quiescent latently infected CD4+ T cells. This reservoir is formed through two processes: i) the infection of resting CD4+ T cells; both naïve and memory, ii) the infection of activated CD4+ T cells which then become quiescent infected cells. One goal of this project was to understand the gene expression changes occurring in naïve CD4+ T cells following activation and subsequent HIV-1 infection and how this may contribute to the establishment of a latent infection in these cells. Utilizing RNA-Seq and a series of validation assays we have identified several genes which are regulated in opposite directions during activation versus infection which we termed DEOC genes. The DEOC genes include a group of physically- and functionally-associated proteins which are key regulators of T cell activation, the cell cycle, cellular proliferation, and cellular quiescence, suggesting that modulation of these DEOC genes may help transition the infected-activated cell from an activated state to a quiescent/resting state to induce a latent infection.